主权项 |
1. A compound of Formula I-A: or a pharmaceutically acceptable salt or prodrug thereof, wherein: R1 and R2 is independently selected from H, —C(J1)2CN, halo, -(L1)n-W, or M; or R1 and R2, taken together with the atoms to which they are bound, form a 5-6 membered aromatic or non-aromatic ring having 0-2 heteroatoms selected from oxygen, nitrogen or sulfur; the ring formed by R1 and R2 is optionally substituted with 0-3 occurrences of JZ; JZ is independently selected from a 3-7 membered fully saturated, partially unsaturated, or aromatic monocyclic ring having 0-2 heteroatoms selected from oxygen, nitrogen or sulfur; or a C1-6aliphatic chain wherein up to three methylene units are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)z—; JZ5 is optionally substituted with 0-3 occurrences of JX; J1 is independently selected from H or C1-2alkyl; or two occurrences of J1, together with the carbon atom to which they are attached, form an optionally substituted 3-4 membered carbocyclic ring; M and L are C1-8aliphatic wherein up to three methylene units are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)z—, each L1 and M are optionally substituted with 0-3 occurrences of JLM; JLM is independently selected from halo, —CN, or a C1-4aliphatic chain wherein up to two methylene units of the aliphatic chain are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)z—; or n is independently selected from 0 or 1; W is independently selected from a 3-7 membered fully saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms selected from oxygen, nitrogen or sulfur; or an 7-12 membered fully saturated, partially unsaturated, or aromatic bicyclic ring having 0-5 heteroatoms selected from oxygen, nitrogen, or sulfur; wherein W is optionally substituted with 0-5 occurrences of JW; JW is independently selected from —CN; halo; —CF3; a C1-4aliphatic wherein up to two methylene units are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)z—; or a 3-6 membered non-aromatic ring having 0-2 heteroatoms selected from oxygen, nitrogen, or sulfur; or two occurrences of JW on the same atom, together with atom to which they are joined, form a 3-6 membered ring having 0-2 heteroatoms selected from oxygen, nitrogen, or sulfur; or two occurrences of JW, together with W, form a 6-10 membered saturated or partially unsaturated bridged ring system; Ring A is independently selected from: R3 is independently selected from -(L2)k-Q1 or T; L2 and T are each independently a C1-10aliphatic chain wherein up to three methylene units of the aliphatic chain are optionally replaced with —O—, —NR—, —S(O)z—, or —C(O)—; each L2 and T is independently substituted with 0-5 occurrences of JLT; JLT is independently selected from halo, —CN, or a C1-4aliphatic chain wherein up to two methylene units of the aliphatic chain are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)z—; k is 0 or 1; Q1 is independently selected from a 3-7 membered fully saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms selected from oxygen, nitrogen or sulfur; or an 7-12 membered fully saturated, partially unsaturated, or aromatic bicyclic ring having 0-5 heteroatoms selected from oxygen, nitrogen, or sulfur; wherein Q1 is independently substituted with 0-5 occurrences of JQ; JQ is independently selected from halo; —CN; ═O; Q2; or a C1-8aliphatic chain wherein up to three methylene units of the aliphatic chain are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)z—; each occurrence of JQ is optionally substituted by 0-3 occurrences of JR; or two occurrences of JQ on the same atom, taken together with the atom to which they are joined, form a 3-6 membered ring having 0-2 heteroatoms selected from oxygen, nitrogen, or sulfur; wherein the ring formed by two occurrences of JQ is optionally substituted with 0-3 occurrences of JX; or two occurrences of JQ, together with Q1, form a 6-10 membered saturated or partially unsaturated bridged ring system; Q2 is independently a 3-7 membered fully saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms selected from oxygen, nitrogen, or sulfur; or a 7-12 membered fully saturated, partially unsaturated, or aromatic bicyclic ring having 0-5 heteroatoms selected from oxygen, nitrogen, or sulfur; JR is independently selected from halo; —CN; ═O; →O; Q3; or a C1-6aliphatic chain wherein up to two methylene units of the aliphatic chain are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)z—; each JR is optionally substituted with 0-3 occurrences of JP; or two occurrences of JR on the same atom, together with the atom to which they are joined, form a 3-6 membered ring having 0-2 heteroatoms selected from oxygen, nitrogen, or sulfur; wherein the ring formed by two occurrences of JR is optionally substituted with 0-3 occurrences of JX; or two occurrences of JR, together with Q2, form a 6-10 membered saturated or partially unsaturated bridged ring system; Q3 is a 3-7 membered fully saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms selected from oxygen, nitrogen, or sulfur; a 7-12 membered fully saturated, partially unsaturated, or aromatic bicyclic ring having 0-5 heteroatoms selected from oxygen, nitrogen, or sulfur; JX is independently selected from halo or a C1-4aliphatic chain wherein up to two methylene units of the aliphatic chain are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)z—; or JP is independently selected from halo; —CN; ═O; a C1-6aliphatic chain wherein up to two methylene units of the aliphatic chain are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)z—; or a 3-6 membered non-aromatic ring having 0-2 heteroatoms selected from oxygen, nitrogen, or sulfur; each JP is optionally substituted with 0-3 JM; or two occurrences of JP on the same atom, together with the atom to which they are joined, form a 3-6 membered ring having 0-2 heteroatoms selected from oxygen, nitrogen, or sulfur; two occurrences of JP, together with Q3, form a 6-10 membered saturated or partially unsaturated bridged ring system; R4 is independently selected from H; halo; —CN; a C1-2alkyl optionally substituted with 0-3 occurrences of fluoro; a C3-6cycloalkyl; a 3-4 membered heterocyclyl; or a C1-3aliphatic chain wherein up to two methylene units of the aliphatic chain are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)z—; JM is independently selected from halo or C1-6aliphatic; z is 0, 1, or 2; p is 0, 1, or 2; and R is independently selected from H or C1-4aliphatic. |